Stable pancytopenia will be produced in splenectomized mice and congenitally asplenic mice by the administration of 89 Strontium, a bone-seeking, beta emitting isotope. The intensity of the pancytopenia will be correlated with the amount of 89 Sr administered. The relationship between the erythropoietin titer and the level of anemia in these pancytopenic mice will be determined. Factors will be sought from the serum of very pancytopenic animals that have stimulatory effects on spleen colony forming units, in vitro colony forming units, erythroid colony forming units, and early erythroid burst formation. The hematopoietic response in 89 Sr-induced pancytopenic mice to hypoxia, erythropoietin, and androgens will be measured. The role of radiation-induced stromal damage in the pathogenesis of the pancytopenia will be explored, and attempts will be made to correct the pancytopenia by replacement with hematopoietic stroma. The importance of this study arises from the serious nature of plastic pancytopenias, preleukemic states, and leukemias of man. By developing and studying the model proposed, it is hoped a better understanding of control of normal hematological proliferation and differentiation and recovery from damage of the hematopoietic system will be forthcoming, and that such knowledge will lead to rational approaches to the treatment of spontaneously occurring and drug-induced or radiation-induced pancytopenia in man.